Sparingly-soluble narcotic zinc tannates cause protracted analgesia in rats

Pain thresholds were determined in rats by the titration foot shock technique for 5–8 days after a single injection of zinc tannate salts of heroin (HZT)—41.0 and 81.9 mg/kg as base, LAAM (LZT)—41.0 and 81.9 mg/kg; and hydromorphone (DZT)—39.9 and 79.8 mg/kg. These zinc salts were synthesized, analyzed, suspended in a slow-release vehicle (SRV), and injected subcutaneously. Body weight and pain threshold of each rat were determined at the same time each day. Serum levels of the hydrolyzed metabolites of heroin were measured periodically in rats which had received similar injections of HZT. Analysis of variance showed that all narcotic preparations, except for low dose HZT, led to a significant ( α = 0.05) elevation of pain threshold above that of the SRV control at 24 hr. Pain thresholds were significantly elevated for 3 days after low dose LZT, 4 days after both doses of DZT and 5 days after high dose LZT. Hydrolyzed heroin metabolites were present in the serum for 7 days after a single injection; at that time no analgesia was evident. The mean body weight of HZT and SRV rats continued to increase, whereas the LZT and DZT groups initially tost weight. This study shows that a single injection of 3 narcotic zinc tannate preparations can induce long-lasting elevations in pain thresholds, but tolerance to the analgesia is evident within days.